Gross Motor Function Measure Evolution Ratio: Use as a Control for Natural Progression in Cerebral Palsy.

OBJECTIVE: To develop a new way to interpret Gross Motor Function Measure (GMFM-66) score improvement in studies conducted without control groups in children with cerebral palsy (CP). DESIGN: The curves, which describe the pattern of motor development according to the children's Gross Motor Function Classification System level, were used as historical control to define the GMFM-66 expected natural evolution in children with CP. These curves have been modeled and generalized to fit the curve to particular children characteristics. SETTING: Research center. PARTICIPANTS: Not applicable. INTERVENTIONS: Not applicable. MEAN OUTCOME MEASURES: Not applicable. RESULTS: Assuming that the GMFM-66 score evolution followed the shape of the Rosenbaum curves, by taking into account the age and GMFM-66 score of children, the expected natural evolution of the GMFM-66 score was predicted for any group of children with CP who were <8 years old. Because the expected natural evolution could be predicted for a specific group of children with CP, the efficacy of a treatment could be determined by comparing the GMFM-66 score evolution measured before and after treatment with the expected natural evolution for the same period. A new index, the Gross Motor Function Measure Evolution Ratio, was defined as follows: Gross Motor Function Measure Evolution Ratio=measured GMFM-66 score change/expected natural evolution. CONCLUSIONS: For practical or ethical reasons, it is almost impossible to use control groups in studies evaluating effectiveness of many therapeutic modalities. The Gross Motor Function Measure Evolution Ratio gives the opportunity to take into account the expected natural evolution of the gross motor function of children with CP, which is essential to accurately interpret the therapy effect on the GMFM-66.

High-sensitivity temperature sensing using higher-order Stokes stimulated Brillouin scattering in optical fiber.

In an effort to reduce the cost of sensing systems and make them more compact and flexible, Brillouin scattering has been demonstrated as a useful tool, especially for distributed temperature and strain sensing (DTSS), with a resolution of a few centimeters over several tens of kilometers of fiber. However, sensing is limited by the Brillouin frequency shift's sensitivity to these parameters, which are of the order of ~1.3 MHz/°C and of ~0.05 MHz/µÎµ for standard fiber. In this Letter, we demonstrate a new and simple technique for enhancing the sensitivity of sensing by using higher-orders Stokes shifts with stimulated Brillouin scattering (SBS). By this method, we multiply the sensitivity of the sensor by the number of the Stokes order used, enhanced by six-fold, therefore reaching a sensitivity of ~7 MHz/°C, and potentially ~0.30 MHz/µÎµ. To do this, we place the test fiber within a cavity to produce a frequency comb. Based on a reference multiorder SBS source for heterodyning, this system should provide a new distributed sensing technology with significantly better resolution at a potentially lower cost than currently available DTSS systems.

Using the gross motor function measure evolution ratio to compare different dosage of hyperbaric treatment with conventional therapies in children with cerebral palsy - could it end the controversy?

The Gross Motor Function Measure is used in most studies measuring gross motor function in children with cerebral palsy. In many studies, including those evaluating the effect of hyperbaric treatment, the Gross Motor Function Measure variations were potentially misinterpreted because of the lack of control groups. The Gross Motor Function Measure Evolution Ratio (GMFMER) uses historical data from the Gross Motor Function Classification System curves and allows to re-analyze previous published studies which used the Gross Motor Function Measure by considering the natural expected evolution of the Gross Motor Function Measure. As the GMFMER is defined by the ratio between the recorded Gross Motor Function Measure score increase and the expected increase attributed to natural evolution during the duration of the study (natural evolution yields a GMFMER of 1), it becomes easy to assess and compare the efficacy of different treatments. Objective: The objective of this study is to revisit studies done with different dosage of hyperbaric treatment and to compare the GMFMER measured in these studies with those assessing the effects of various recommended treatments in children with cerebral palsy. Methods: PubMed Searches were conducted to included studies that used the Gross Motor Function Measure to evaluate the effect of physical therapy, selective dorsal rhizotomy, botulinum toxin injection, hippotherapy, stem cell, or hyperbaric treatment. The GMFMER were computed for each group of the included studies. Results: Forty-four studies were included, counting 4 studies evaluating the effects of various dosage of hyperbaric treatment in children with cerebral palsy. Since some studies had several arms, the GMFMER has been computed for 69 groups. The average GMFMER for the groups receiving less than 2 h/week of physical therapy was 2.5 ± 1.8 whereas in context of very intensive physical therapy it increased to 10.3 ± 6.1. The GMFMER of stem cell, selective dorsal rhizotomy, hippotherapy, and botulinum toxin treatment was, 6.0 ± 5.9, 6.5 ± 2.0, 13.3 ± 0.6, and 5.0 ± 2.9, respectively. The GMFMER of the groups of children receiving hyperbaric treatment were 28.1 ± 13.0 for hyperbaric oxygen therapy and 29.8 ± 6.8 for hyperbaric air. Conclusion: The analysis of the included studies with the GMFMER showed that hyperbaric treatment can result in progress of gross motor function more than other recognized treatments in children with cerebral palsy.

A birefringent spectral demultiplexer enables fast hyper-spectral imaging of protoporphyrin IX during neurosurgery.

Hyperspectral imaging and spectral analysis quantifies fluorophore concentration during fluorescence-guided surgery1-6. However, acquisition of the multiple wavelengths required to implement these methods can be time-consuming and hinder surgical workflow. To this end, a snapshot hyperspectral imaging system capable of acquiring 64 channels of spectral data simultaneously was developed for rapid hyperspectral imaging during neurosurgery. The system uses a birefringent spectral demultiplexer to split incoming light and redirect wavelengths to different sections of a large format microscope sensor. Its configuration achieves high optical throughput, accepts unpolarized input light and exceeds channel count of prior image-replicating imaging spectrometers by 4-fold. Tissue-simulating phantoms consisting of serial dilutions of the fluorescent agent characterize system linearity and sensitivity, and comparisons to performance of a liquid crystal tunable filter based hyperspectral imaging device are favorable. The new instrument showed comparable, if not improved, sensitivity at low fluorophore concentrations; yet, acquired wide-field images at more than 70-fold increase in frame rate. Image data acquired in the operating room during human brain tumor resection confirm these findings. The new device is an important advance in achieving real-time quantitative imaging of fluorophore concentration for guiding surgery.

First experience imaging short-wave infrared fluorescence in a large animal: indocyanine green angiography of a pig brain.

The potential to image subsurface fluorescent contrast agents at high spatial resolution has facilitated growing interest in short-wave infrared (SWIR) imaging for biomedical applications. The early but growing literature showing improvements in resolution in small animal models suggests this is indeed the case, yet to date, images from larger animal models that more closely recapitulate humans have not been reported. We report the first imaging of SWIR fluorescence in a large animal model. Specifically, we imaged the vascular kinetics of an indocyanine green (ICG) bolus injection during open craniotomy of a mini-pig using a custom SWIR imaging instrument and a clinical-grade surgical microscope that images ICG in the near-infrared-I (NIR-I) window. Fluorescence images in the SWIR were observed to have higher spatial and contrast resolutions throughout the dynamic sequence, particularly in the smallest vessels. Additionally, vessels beneath a surface pool of blood were readily visualized in the SWIR images yet were obscured in the NIR-I channel. These first-in-large-animal observations represent an important translational step and suggest that SWIR imaging may provide higher spatial and contrast resolution images that are robust to the influence of blood.

Optimal wavelength selection for optical spectroscopy of hemoglobin and water within a simulated light-scattering tissue.

An algorithm that selects optimal wavelengths for spectral fitting of diffuse light reflectance spectra using a nonnegative least squares method is presented. Oxyhemoglobin, deoxyhemoglobin, and water are considered representative absorbers, but the approach is not constrained or limited by absorber selection provided native basis spectra are available. The method removes wavelengths iteratively from a scattering-modulated absorption matrix by maximizing the product of its singular values and offers considerable improvements over previously published wavelength selection schemes. Resulting wavelength selections are valid for a broad range of optical properties and yield lower RMS errors than other wavelength combinations. The method is easily modified and broadly applicable to tissue optical spectroscopy. Adaptation of the algorithm to select optimal light-emitting diodes for fitting blood is described.

Red-light excitation of protoporphyrin IX fluorescence for subsurface tumor detection.

OBJECTIVE The objective of this study was to detect 5-aminolevulinic acid (ALA)-induced tumor fluorescence from glioma below the surface of the surgical field by using red-light illumination. METHODS To overcome the shallow tissue penetration of blue light, which maximally excites the ALA-induced fluorophore protoporphyrin IX (PpIX) but is also strongly absorbed by hemoglobin and oxyhemoglobin, a system was developed to illuminate the surgical field with red light (620-640 nm) matching a secondary, smaller absorption peak of PpIX and detecting the fluorescence emission through a 650-nm longpass filter. This wide-field spectroscopic imaging system was used in conjunction with conventional blue-light fluorescence for comparison in 29 patients undergoing craniotomy for resection of high-grade glioma, low-grade glioma, meningioma, or metastasis. RESULTS Although, as expected, red-light excitation is less sensitive to PpIX in exposed tumor, it did reveal tumor at a depth up to 5 mm below the resection bed in 22 of 24 patients who also exhibited PpIX fluorescence under blue-light excitation during the course of surgery. CONCLUSIONS Red-light excitation of tumor-associated PpIX fluorescence below the surface of the surgical field can be achieved intraoperatively and enables detection of subsurface tumor that is not visualized under conventional blue-light excitation. Clinical trial registration no.: NCT02191488 (clinicaltrials.gov).

Sensorimotor adaptation of whole-body postural control.

The aim of the present study was to examine the modification of postural symmetry during quiet standing using a sensorimotor adaptation paradigm. A group of neurologically typical adult participants performed a visually guided mediolateral (left-right) weight shifting task requiring precise adjustments in body orientation. During one phase of the task, the visual feedback of center of pressure (COP) was systematically biased toward the left or the right, requiring an adjustment in posture to compensate. COP during quiet standing without visual feedback was examined prior to and immediately following the sensorimotor adaptation procedure, in order to observe whether compensatory adjustments in postural control resulting from the visual-feedback manipulation would transfer to the control of whole-body COP during quiet standing. Results showed that the sensorimotor adaptation procedure induced a small but reliable compensatory change in the stance of participants, resulting in a change in postural symmetry and control that was found to persist even after normal visual feedback was restored.

Characterization and standardization of tissue-simulating protoporphyrin IX optical phantoms.

Optical devices for measuring protoporphryin IX (PpIX) fluorescence in tissue are routinely validated by measurements in optical phantoms. Yet there exists limited data to form a consensus on the recipe for phantoms that both mimic the optical properties found in tissue and yield a reliable and stable relationship between PpIX concentration and the fluorescence remission intensity. This study characterizes the influence of multiple phantom components on PpIX fluorescence emission intensity, using Intralipid as the scattering source, bovine whole blood as the background absorber, and Tween as a surfactant to prevent PpIX aggregation. Optical measurements showed a linear proportionality (r > 0.99) between fluorescence intensity and PpIX concentration (0.1 to 10 µg/mL) over a range of Intralipid (1 to 2%) and whole blood (0.5 to 3%) for phantoms containing low surfactant (≤ 0.1%), with fluorescence intensities and scattering and absorption properties stable for 5 h after mixing. The role of surfactant in PpIX phantoms was found to be complex, as aggregation was evident in aqueous nonturbid phantoms with no surfactant (0% Tween), and avoided in phantoms containing Intralipid as the scattering source with no additional or low amounts of added surfactant (≤ 0.1% Tween). Conversely, phantoms containing higher surfactant content (>0.1% Tween) and whole blood showed interactions that distorted the fluorescence emissions.